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Omega-3 Fatty Acids in Preventing Joint Symptoms in Patients With Stage I-III Breast Cancer Receiving Anastrozole, Exemestane, or Letrozole

Primary Purpose

Recurrent Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
omega-3 fatty acid supplement
Placebo
Clinical assessments
Assessment of therapy complications
Magnetic Resonance Imaging
Correlative/special studies
Sponsored by
Ohio State University Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Recurrent Breast Cancer focused on measuring Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Women diagnosed with breast cancer stages I-III initiating first adjuvant AI therapy with any of the Food and Drug Administration- (FDA) approved AIs (anastrozole, exemestane, letrozole)
  • Concurrent gonadotropin-releasing hormone (GnRH) agonist therapy is allowed
  • Concurrent breast related radiation therapy is allowed
  • Prior tamoxifen use is allowed
  • Prior chemotherapy is allowed
  • History of osteoarthritis and/or fibromyalgia is allowed
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Metastatic malignancy of any kind
  • Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease, with the exception of osteoarthritis and fibromyalgia
  • AI use > 2 weeks prior to study enrollment
  • Known bleeding disorders
  • History of diabetes mellitus, heart disease or TIA/stroke
  • Current use of warfarin or other anticoagulants
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,or psychiatric illness/social situation that would limit compliance with study requirements
  • Daily use of n-3 PUFA concentrates or capsules or regular or any other supplements that might interact with n-3 PUFA supplements within six months of study initiation; sporadic use of n-3 PUFA supplement may be eligible if there has been a 3-month washout period prior to randomization
  • Pregnant or nursing women
  • Known sensitivity or allergy to fish or fish oil
  • Concurrent use of daily full dose aspirin (≥ 325 mg/day), nonsteroidal anti-inflammatory drugs (NSAIDs) or NSAID-containing products or steroids; one month washout period is required prior to randomization
  • Unable to give informed consent
  • In patients consenting for optional MRIs, any contraindication to MRI examination including but not limited to ferromagnetic metal in the body, pacemaker, or severe claustrophobia

Sites / Locations

  • Ohio State University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm I (omega-3 fatty acid supplement)

Arm II (placebo)

Clinical Assessments

Assessment of therapy complications

Magnetic Resonance Imaging

Correlative/special studies

Arm Description

Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA)

Typical American Diet oils (TAD)

Brief Pain Inventory (BPI), Stanford's Health Assessment-Disability Index (HAS), FACT-B and endocrine subscale (FACT-ES)

Adverse events will be monitored by self-reporting of signs and symptoms. Patients will maintain a daily diary of time of supplement intake and any possible ill effects, with instructions to contact the PI or Research Nurse to discuss and manage any possible side effects.

Optional bilateral hand and wrist MRI imaging will be obtained

Enrolled participants will have peripheral blood samples drawn for plasma and RBC n-3 PUFA levels within 4 weeks of starting AI therapy.

Outcomes

Primary Outcome Measures

Pain score change after 6 months (6 months -baseline) based on the FACT-B/ES instrument
Pain scores based on FACT-B/ES, HAS and BPI will be plotted over time for each arm. Agreement between HAS, BPI-short and FACT-B/ES evaluated using Altman and Bland plot after proper data transformation. Also, Linear Mixed model used to explore if the pain scores are different at 3 and 6 months. Logistic regression models used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups, with potential covariates including age, body mass index, baseline pain scores (0 month), prior chemotherapy and other variables.

Secondary Outcome Measures

Pain score change after 6 months (6 months -baseline) based on the HAS and BPI instruments
Agreement between HAS, BPI-short and FACT-B/ES evaluated using Altman and Bland plot after proper data transformation. Also, Linear Mixed model used to explore if the pain scores are different at 3 and 6 months. Logistic regression models used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups, with potential covariates including age, body mass index, baseline pain scores (0 month), prior chemotherapy and other variables.
Compliance rates with oral supplements (omega-3 fatty acid and placebo)
Feasibility of using the instruments HAS, BPI-short, FACT-B/ES for the assessment of joint symptoms
Effectiveness of blinding
Summarized using a Chi-square test.
Correlation of guess with pain scores
Checked using logistic models to see if treatment guesses are explained by the patient's awareness of clinical benefit.
Relationship between serum and RBC omega-3 fatty acid levels, inflammatory blood markers and MRI changes and the joint symptoms
Scatter plots and correlation coefficients (either Pearson or Spearman) will be used to summarize their pair wise relation. The differences between the treatment and placebo in terms of these measures will also be reported using numerical summaries and graphic plots.

Full Information

First Posted
November 14, 2011
Last Updated
February 24, 2023
Sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
Cancer and Leukemia Group B
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1. Study Identification

Unique Protocol Identification Number
NCT01478477
Brief Title
Omega-3 Fatty Acids in Preventing Joint Symptoms in Patients With Stage I-III Breast Cancer Receiving Anastrozole, Exemestane, or Letrozole
Official Title
Prevention of Aromatase Inhibitor-Induced Joint Symptoms With Omega 3 Fatty Acid Supplementation: a Randomized Placebo Controlled Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
October 4, 2011 (Actual)
Primary Completion Date
January 9, 2014 (Actual)
Study Completion Date
January 9, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
Cancer and Leukemia Group B

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized pilot trial studies omega-3 fatty acid in preventing joint symptoms in patients with stage I-III breast cancer receiving anastrozole, exemestane, or letrozole. Omega-3 fatty acid supplement may lessen or prevent joint stiffness or pain in patients receiving hormone therapy for breast cancer.
Detailed Description
OBJECTIVES: I. To assess the feasibility of evaluating joint symptoms in postmenopausal women with breast cancer randomized to n-3 PUFA (omega-3 fatty acid) vs. placebo supplementation using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and endocrine subscale (FACT-ES), Brief Pain Inventory (BPI) and Stanford's Health Assessment -Disability Index (HAS) during the first 6 months of adjuvant aromatase inhibitor (AI) therapy. II. To preliminarily evaluate the efficacy of n-3 PUFA vs. placebo supplementation on AI induced joint symptoms. III. To explore blood and imaging based biomarkers (plasma and red blood cell [RBC] levels of n-3 PUFAs, inflammatory cytokines and receptors, and intra-articular tenosynovial inflammation by musculoskeletal magnetic resonance imaging [MRI] imaging) of AI-induced joint symptoms in women on AI therapy randomized to n-3 PUFAs vs. placebo supplementation. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive omega-3 fatty acid orally (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
Keywords
Breast Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (omega-3 fatty acid supplement)
Arm Type
Experimental
Arm Description
Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA)
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Typical American Diet oils (TAD)
Arm Title
Clinical Assessments
Arm Type
Experimental
Arm Description
Brief Pain Inventory (BPI), Stanford's Health Assessment-Disability Index (HAS), FACT-B and endocrine subscale (FACT-ES)
Arm Title
Assessment of therapy complications
Arm Type
Experimental
Arm Description
Adverse events will be monitored by self-reporting of signs and symptoms. Patients will maintain a daily diary of time of supplement intake and any possible ill effects, with instructions to contact the PI or Research Nurse to discuss and manage any possible side effects.
Arm Title
Magnetic Resonance Imaging
Arm Type
Experimental
Arm Description
Optional bilateral hand and wrist MRI imaging will be obtained
Arm Title
Correlative/special studies
Arm Type
Experimental
Arm Description
Enrolled participants will have peripheral blood samples drawn for plasma and RBC n-3 PUFA levels within 4 weeks of starting AI therapy.
Intervention Type
Dietary Supplement
Intervention Name(s)
omega-3 fatty acid supplement
Other Intervention Name(s)
fish oil, omega fatty acid, O3FA, MNSG-194®, n-3 PUFA supplementation
Intervention Description
6 capsules per day (4.3 g)x 6 months
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
PLCB, Typical American Diet oils, TAD
Intervention Description
6 capsules per day (4.3 g)x 6 months. Supplement should be taken with food once per day. No specific food requirements are needed.
Intervention Type
Other
Intervention Name(s)
Clinical assessments
Other Intervention Name(s)
Brief Pain Inventory, BPI, Stanford's Health Assessment-Disability Index, HAS, FACT-B and endocrine subscale, FACT-ES
Intervention Description
All three instruments will be administered at baseline, at 3 months, 6 months and at additional time intervals when there is a significant change in therapy (discontinuation/switch, pain medication administration) during routine medical oncology visits.
Intervention Type
Other
Intervention Name(s)
Assessment of therapy complications
Other Intervention Name(s)
adverse events, toxicities, Expected Toxicities, Potential Toxicities
Intervention Description
Severity/grade of reaction according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
MRI, NMR imaging, NMRI, nuclear magnetic resonance imaging
Intervention Description
Optional bilateral hand and wrist MRI imaging will be obtained at baseline and at 6 months to eligible patients who have no contraindications to MRI imaging.
Intervention Type
Procedure
Intervention Name(s)
Correlative/special studies
Other Intervention Name(s)
laboratory studies
Intervention Description
Plasma, RBC, and serum samples from the baseline blood draw will also be stored at -70C for fatty acid and biomarker analyses and repeated at 3 month and 6 month intervals. Samples will be analyzed in batches every 6 months.
Primary Outcome Measure Information:
Title
Pain score change after 6 months (6 months -baseline) based on the FACT-B/ES instrument
Description
Pain scores based on FACT-B/ES, HAS and BPI will be plotted over time for each arm. Agreement between HAS, BPI-short and FACT-B/ES evaluated using Altman and Bland plot after proper data transformation. Also, Linear Mixed model used to explore if the pain scores are different at 3 and 6 months. Logistic regression models used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups, with potential covariates including age, body mass index, baseline pain scores (0 month), prior chemotherapy and other variables.
Time Frame
baseline, 6 months
Secondary Outcome Measure Information:
Title
Pain score change after 6 months (6 months -baseline) based on the HAS and BPI instruments
Description
Agreement between HAS, BPI-short and FACT-B/ES evaluated using Altman and Bland plot after proper data transformation. Also, Linear Mixed model used to explore if the pain scores are different at 3 and 6 months. Logistic regression models used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups, with potential covariates including age, body mass index, baseline pain scores (0 month), prior chemotherapy and other variables.
Time Frame
baseline, 6 months
Title
Compliance rates with oral supplements (omega-3 fatty acid and placebo)
Time Frame
baseline, 6 months
Title
Feasibility of using the instruments HAS, BPI-short, FACT-B/ES for the assessment of joint symptoms
Time Frame
baseline, 6 months
Title
Effectiveness of blinding
Description
Summarized using a Chi-square test.
Time Frame
baseline, 6 months
Title
Correlation of guess with pain scores
Description
Checked using logistic models to see if treatment guesses are explained by the patient's awareness of clinical benefit.
Time Frame
baseline, 6 months
Title
Relationship between serum and RBC omega-3 fatty acid levels, inflammatory blood markers and MRI changes and the joint symptoms
Description
Scatter plots and correlation coefficients (either Pearson or Spearman) will be used to summarize their pair wise relation. The differences between the treatment and placebo in terms of these measures will also be reported using numerical summaries and graphic plots.
Time Frame
baseline, 6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Women diagnosed with breast cancer stages I-III initiating first adjuvant AI therapy with any of the Food and Drug Administration- (FDA) approved AIs (anastrozole, exemestane, letrozole) Concurrent gonadotropin-releasing hormone (GnRH) agonist therapy is allowed Concurrent breast related radiation therapy is allowed Prior tamoxifen use is allowed Prior chemotherapy is allowed History of osteoarthritis and/or fibromyalgia is allowed Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Metastatic malignancy of any kind Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease, with the exception of osteoarthritis and fibromyalgia AI use > 2 weeks prior to study enrollment Known bleeding disorders History of diabetes mellitus, heart disease or TIA/stroke Current use of warfarin or other anticoagulants Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,or psychiatric illness/social situation that would limit compliance with study requirements Daily use of n-3 PUFA concentrates or capsules or regular or any other supplements that might interact with n-3 PUFA supplements within six months of study initiation; sporadic use of n-3 PUFA supplement may be eligible if there has been a 3-month washout period prior to randomization Pregnant or nursing women Known sensitivity or allergy to fish or fish oil Concurrent use of daily full dose aspirin (≥ 325 mg/day), nonsteroidal anti-inflammatory drugs (NSAIDs) or NSAID-containing products or steroids; one month washout period is required prior to randomization Unable to give informed consent In patients consenting for optional MRIs, any contraindication to MRI examination including but not limited to ferromagnetic metal in the body, pacemaker, or severe claustrophobia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicole Williams, MD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29233615
Citation
Orchard TS, Andridge RR, Yee LD, Lustberg MB. Diet Quality, Inflammation, and Quality of Life in Breast Cancer Survivors: A Cross-Sectional Analysis of Pilot Study Data. J Acad Nutr Diet. 2018 Apr;118(4):578-588.e1. doi: 10.1016/j.jand.2017.09.024. Epub 2017 Dec 9.
Results Reference
derived
Links:
URL
http://cancer.osu.edu
Description
Jamesline

Learn more about this trial

Omega-3 Fatty Acids in Preventing Joint Symptoms in Patients With Stage I-III Breast Cancer Receiving Anastrozole, Exemestane, or Letrozole

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